BACKGROUND The first Spanish series of spontaneous infectious mononucleosis (IM) by cytomegalovirus (CMV) in immunocompetent adults is reported. METHODS Patients whose clinical manifestations, physical exam, analysis and serology were compatible with acute CMV infection from 1984 to 1993 were retrospectively reviewed. RESULTS Thirty patients with a mean age of 36 years fulfilled the diagnostic criteria. All presented fever, alone or associated with other symptoms, with a mean duration of 18 days, which persisted over 3 weeks in 36%. Physical exam showed lymph node enlargement (50%), hepatomegaly (33%), splenomegaly (20%) and was normal in 8 patients (26%). Mean leukocyte count was 9.75 x 10(9) (+/- 4.63 x 10(9) with more than 50% lymphomonocytic cells in 22 patients (76%) and reactive lymphocytes, principally from the outset, although this was observed on days 2 and 60 in 11 cases (36%). LDH, ASAT and ALAT were moderately elevated and ESR was normal. Serologic diagnosis was established from IgM (13%) seroconversion or positive IgM in the two samples with IgG four-fold increase (23%), as well as the presence of positive IgM and invariable high IgG in both determinations (26%) or all IgM positive titers in a single sample (36%). CONCLUSIONS Infectious mononucleosis by cytomegalovirus is an infrequently diagnosed disease which should be considered in any young patient with fever despite a little demonstrative initial physical exam absence of atypical lymphocytes or a lack of diagnostic serology.